Mitochondrial

Alpha-lipoic acid (ALA) is a sulfur-containing mitochondrial cofactor, used as a racemic drug for the pain and pins-and-needles of diabetic nerve damage. Meta-analyses of randomised trials support it for diabetic neuropathy symptoms. Its effects on weight and blood sugar are real but small. Supplements come as the racemic mix, as pure R-ALA, or as Na-R-ALA, a sodium salt of R-ALA made to absorb better.

ATX-304, formerly O304, is a pan-AMPK activator from Betagenon developed as a type 2 diabetes drug and exercise mimetic. In a phase IIa trial in people with type 2 diabetes already on metformin, it lowered fasting glucose and insulin resistance and improved microvascular perfusion. Newer mouse work extends it to fatty liver and kidney injury. The developer's patents describe a milled sodium salt: in volunteers, a quarter of the dose matched the blood levels of the original suspension, partly because of the salt and partly because of the milling.

BAM15 is a mitochondrial uncoupler. It lets protons leak back into mitochondria so fuel is burned without making ATP, and unlike older uncouplers it does not depolarise the cell's outer membrane. In obese mice it reduced fat mass and improved insulin sensitivity without changing food intake, lean mass or body temperature. It has not been tested in humans.

Coenzyme Q10 (CoQ10) is part of the mitochondrial energy chain and one of the most widely used supplements. Its best evidence is in chronic heart failure. There, the Q-SYMBIO trial found fewer major cardiovascular events and deaths over two years. For statin muscle pain, migraine and blood pressure, the results are mixed or modest.

PQQ (pyrroloquinoline quinone) is a redox cofactor first found in bacteria. Mammals do not make it but take in trace amounts from food. In cells it switches on mitochondrial biogenesis through the PGC-1α pathway. In humans, small 12-week trials of PQQ disodium salt reported better memory and attention scores.

SANA is a nitroalkene derivative of salicylate, the parent of aspirin, developed for obesity and type 2 diabetes. In obese mice it reduced weight, liver fat and insulin resistance by raising creatine-dependent energy expenditure in fat tissue. MVD1 is the name its first human trial ran under. That trial was a small, 15-day phase 1 study, which reported good tolerability and early effects on body weight and glucose.

SLU-PP-332 is a synthetic agonist of all three estrogen-related receptors (ERRα, β and γ), strongest at ERRα, and the best-known "exercise mimetic" research compound. In mice it switched on an aerobic exercise gene program, increased oxidative muscle fibres and improved endurance. In obese mice it raised energy expenditure and fat oxidation and reduced fat mass. It has never been tested in humans.

SLU-PP-915 is a pan-ERR agonist from the lab that made slu-pp-332. It is a chemically distinct thiophene boronic acid and, unlike SLU-PP-332, it is orally bioavailable. In mice it improved aerobic exercise performance as much as SLU-PP-332 did and protected the heart in a heart-failure model. It has never been tested in humans.

Ubiquinol is the reduced, electron-carrying form of coenzyme-q10, sold as a better-absorbed version. One small study found it raised blood CoQ10 more than ubiquinone. A randomised crossover study in older adults found no significant difference. Its most notable trial is in multiple-system atrophy, where high doses improved a motor score.